Anemias
中国医科大学附属第一医院血液科 李艳
CUF-S (造血干 C,红系祖 C)
↓
proerythroblast ( 原始 RBC)
↓
Basophilic normoblast ( 早幼 RBC)
↓
Polychromatic mormoblast( 中幼 RBC)
↓
Orthrochromatic normoblast ( 晚幼 RBC) 此阶段脱
核进入血循环
↓
Reticulocyte (网织 RBC)
经特殊染色见到丝状或网状结构,保留残余线粒体
和核糖,仍有继续合成 Hb的能力(从早幼 RBC开始)
↓
erythrocyte
Definition
? A reduction below normal in the
concentration of hemoglobin,the
mass of red blood cells and/or the
hematocrit in the blood.
In men Hb < 120g/L
RBC <4.5× 1012/L
HCT <0.42
In women Hb < 110g/L
RBC<4.0 × 1012/L
HCT<0.37
Factors influencing Hb
concentration
Sex
Age
Altitude
Alterations in plasma volume
★ Classification
Morphologic classification
Type MCV(um) MCH(PG) MCHC(%) Diagnosis
Macrocytic > 100 > 32 32-35 Megaloblastic
anemia
Normocytic 80-100 26-32 32-35 AA,HA,Acute
posthemorragic
anemia
Microcytic < 80 < 26 < 32 IDA,
Sideroblastic
anemia
Thalassemias
Kinetic classification
(Classified according to etiology and
pathogenesis)
一, Decreased erythropoiesis
1 Proliferation and differentiation
abnormalities of SC
HSC,AA,Fanconis anemia,MDS
Erythrocytic progenitors, Pure red cell aplasia,
Anemias caused by kidney failure
and endocrine disorders
2 Marrow infiltration
leukemias
carcinoma
multiple myeloma
myelofibrosis
Malignant histocytosis
3 Production and maturation blockages
of differentiating cells
DNA synthesis blockage, Vit B12,falic
acid difficiencies,嘌呤和嘧啶
metabolic defects→Megaloblastic
anemia
Hb synthesis blockage,
Heme production defect, IDA
Heptoglobin production defect,
Thalassemias
4 Unknown reason or several
mechanisms
Sideroblastic anemia
Chronic disease anemias (chronic
inflummation,infections,尿毒症,
Hepatic disorders,neoplasm,
connective tissue disease,endocrine
disorders)
二,Accelerated destruction of red cells
1) Endogenous (intra-erythrocyte defects)
1.Membrane defects of erythrocytes,
Hereditary,Hereditary spherocytosis (HS)
Hereditasy elliplocytosis (HE)
Acquired, PNH
2.Enzyme defects
Glucose--6--Phosphate Dehydrogenase
(G6PD) deficiency
Pyruvate kinase deficiency
3.Abnormal haptogllbin synthesis,
Sickle cell anemia,Hemoglobinopathies
Thalassemias
2)Extragenous
1,Immune HA, AIHA,neonatal HA,mismatched
transfusion,drug-induced HA
2,Mechanical, march hemoglobinuria,cardiac
valves prostheses,microangiopathic hemolytic
disorders.
3,Due to chemical,physical or microrganisms,
Chemical toxin-and drug-induced hemolysis,
large scale burned patient (severe burned patient)
Infection-induced,benzene,radiation
microrganisms,Malaria,virus,etc.
4,Increased damage of monocyte-macrocyte system,
Hypersplenism
三, Blood loss
◆ Acute posthemorrage anemia
◆ Chronic bleeding →IDA
Classified accordind to the
proliferative situations of BM
Hyperplastic anemias (增生性贫血 ):
Hemolytic anemia
Anemia caused by blood loss
Megaloblastic anemia,IDA
Hypoplastic anemias (增生减低性贫血 ),AA
Clinical manifestations
Factors influencing symptoms:
Severity of anemia
Hb<80~90g/L→symptoms
Rapidity of anemia
Abrupt loss of 20% of the circulating
blood volume → marked pallor,
postural hypotension and tachycardia
(心动过速 )
The loss of 50% → severe shock even
dealth.
In contrast,the gradual loss
(even Hb 30~40g/L) of the
circulating red cell mass in a
patient with pernicious anemia
may occur without any
symptoms at all.
Why?
? Red cell 2,3 DPG
(RBC内 2,3-二磷酸甘油酸) ↑
In anemia the oxyhemoglobin dissociation curve
usually shifts (右移 ) in a manner to increase the
quantity of oxygen released in tissues without
oppeciably altering the quantity of osygen bound in
the lungs,Red cell 2,3 diphophoglycerate (2,3 DPG)
regularly increases in anemic patients to mediate
this effect,Maximum elevation of RBC 2,3 DPG
increases oxygen delivery only about 30 per cent,
but this is a highly efficient form of compensation
requiring no significant expenditure of energy.
The aged patients or patients
with vascular or cardiac diseases
may not stand to milder anemia.
The level of anemia at which
symptoms occur is highly variable
among individuals as would be
expected from the widely differing
degrees of physical activity,physical
conditioning,circulatory adequacy,
and sensitivity or stoicism of the
population,
1,General manifestations:
(Nonspecific and reflect tissue hypoxia)
Tiredness,fatigue→ the most common,the
earliest symptom
Pallor of skin and mucosa→shared
chracteristic
2, Cardiovascular systems,
Palpitations and dyspnea on exertion,
breathlessness→common symptoms
Valvulae murmurs
Hb <30g/L,>3m→Anemic cardic disease
3,Neurologic system,
Headache,Dizziness,Confusion,decreased
mental acuity (记忆力衰退 ),晕厥,注意力
不集中,失眠,耳鸣.
severe anemia→Coma
4, Digestive system:
Anorexia (食欲不振 ),厌食 →early
megaloblastic anemia
Nausea(恶心 ),flatulence(胀气 ),
diarrhoea(腹泻 ) or constipation (便秘 )
lingual abnormalities (舌的改变 ),common
5,Genitourinary system:
severe anemia→ polyurea (多尿 ),
hypobaric urine (尿比重低 ),
proteinuria (蛋白尿 ),肾小球滤过功能和小
管分泌及回收功能障碍
female:disturbed menstruation (月经紊
乱 ),性功能减退多见
6,Other:
7,Manifestations of underlying disease:
The process of correct diagnosis is the
one of differential diagnosis.
Steps,1,To Establish the type of
anemia
2,To find out the cause or
underlying diseases of anemia
Diagnosis
1,Cause or inducer of anemia:
Nutrition,special habits for food change in
stool habits,stool Guaiacs in all
profession
influation of surrounding environment
chronic diseases
menstruation,marriage
一,History
2,Developing processes,severity
& complications of anemias
Duration and onset of symptoms
3.Important laboratory results,
diagnosis,treatments and their
effects.
skin and mucosa,pallor,jaundice,
petechiae
hair and nails
adenopathy (淋巴结肿大 )
hepatomegaly-splenomegaly
neurologic abnormalities
肛门及妇科盆腔检查
二,Physical examination
1,The hemogram ( 血像)
Routine blood exam(Hb,RBC)
The reticulocyte count (RC)
RC↑:hyperplastic
RC↓:hypoplastic
三,Laboratory findings
Reticulocyte Count
? Normal,0.002-0.015
? Is required in the evaluation of all patients
with anemia as it is a simple measure of
production
? Young RBC that still contains a small amount
of RNA
? Normally take 1 day for reticulocyte to mature,
Under influence of epo takes 2-3 days
? 1/120th of RBC normally
Absolute Retic count
? Retic counts are reported as a percentage,
RBC count x Retic % = Absoulte retic count
normal,(77+23) x 109/L
? Absolute Retic counts need to be corrected
for early release ( If polychromasia is present)
? Absolute retic/2 (for hct in mid 20’s)
? Absolute retic/3 (hct <20)
MCV(the mean corpuscular volume),the
most useful of the RBC indices.
MCH,MCHC,are rarely as helpful as the
MCV
The leukocyte and platelet count,
Anemia with a diminished
leukocyteand platelet count-pancytopenia-
suggests either primary marrow disease,
megaloblastic anemia,or hypersplenism.
Examination of the peripheral blood smear:
2,Examination of bone marrow
骨髓涂片检查:主要观察 BM增生程度,各系统细胞分类
计数,异常细胞,正常 BM组织有核细胞与脂肪组织各占
1/2,前者增多(尤其是红系)见于增生性贫血,后者增
多代表 BM增生低下,见于 AA,骨髓小粒是血液稀释与
否的一个重要标志。
Examination of aspirated smears in general gives
superior cytologic information while the core
biopsy provides crucial information concerning
the overall cellularity,as well as the presence of
fibrosis,tumor,or granulomas,Both procedures
are complemantary and are best performed
together when the diagnosis is in doubt,Bone
marrow iron staining
3,Some useful ancillary tests
1) Stools for occult blood
2) Tests for hemolytic anemia such as
Coombs’test
3) Tests for nutritional anemia such as serum
folic acid,serum Vitamin B12,SI,SF,etc.
4) Liver and kidney function tests
5) Immunologic tests
6) 影像学检查:钡餐透视,钡灌肠
Treatment
一,Treatment of the causes
The purpose is the treatment
of the underlying disease.
Gastric cancer→Pernicious anemia( 恶性贫血)
( megaloblastic anemia)
二,Drugs
明确病因之前且忌乱投药
? Iron agents; calculation of dose
? falic acid,Vit B12
? Vit B6
? Corticosteroids, AIHA,AA,PNH
? Androgens,may promate reythropoiesis,
1.)刺激 EPO分泌。 2)增强 BM对 EPO的效应。
? EPO,Anemia caused by kidney diseases
? Immunosuppression agents
ALG (antilymphocyte globulin)
CsA,Acute and severe AA
三,Transfusions
Avoid of complications as hepatitis
and AIDS
? Whole blood
? Frozed red cells
? Washed red cells
? Leukocyte poor packed cells ( 浓缩 RBC)
Chronic anemia, Hb<60g/L→Transfusion
Hereditary spherocytosis
AIHA
Hypersplenism
由于胸腺瘤 (Thymoma)引起的纯红 AA,
切除胸腺可使部分患者病情缓解。
Chronic ITP
四,(Operation) Splenectomy
五,BMT( bone marrow
transplantation)
? SAA
? MDS
Lab Evaluation of
Hypoproliferative Anemias
Fe TIBC Ferritin
Fe Deficiency low High(>300) low
Anemia of
Chronic Dx
low low Normal to
high
Aplastic anemia High Extremely
high
Normal to
high
Laboratory findings in anaemia
Drs Shepherd,Dexter,and
Rapson Spring 2001
Scanning Electron microscopy:
normal red cell
中国医科大学附属第一医院血液科 李艳
CUF-S (造血干 C,红系祖 C)
↓
proerythroblast ( 原始 RBC)
↓
Basophilic normoblast ( 早幼 RBC)
↓
Polychromatic mormoblast( 中幼 RBC)
↓
Orthrochromatic normoblast ( 晚幼 RBC) 此阶段脱
核进入血循环
↓
Reticulocyte (网织 RBC)
经特殊染色见到丝状或网状结构,保留残余线粒体
和核糖,仍有继续合成 Hb的能力(从早幼 RBC开始)
↓
erythrocyte
Definition
? A reduction below normal in the
concentration of hemoglobin,the
mass of red blood cells and/or the
hematocrit in the blood.
In men Hb < 120g/L
RBC <4.5× 1012/L
HCT <0.42
In women Hb < 110g/L
RBC<4.0 × 1012/L
HCT<0.37
Factors influencing Hb
concentration
Sex
Age
Altitude
Alterations in plasma volume
★ Classification
Morphologic classification
Type MCV(um) MCH(PG) MCHC(%) Diagnosis
Macrocytic > 100 > 32 32-35 Megaloblastic
anemia
Normocytic 80-100 26-32 32-35 AA,HA,Acute
posthemorragic
anemia
Microcytic < 80 < 26 < 32 IDA,
Sideroblastic
anemia
Thalassemias
Kinetic classification
(Classified according to etiology and
pathogenesis)
一, Decreased erythropoiesis
1 Proliferation and differentiation
abnormalities of SC
HSC,AA,Fanconis anemia,MDS
Erythrocytic progenitors, Pure red cell aplasia,
Anemias caused by kidney failure
and endocrine disorders
2 Marrow infiltration
leukemias
carcinoma
multiple myeloma
myelofibrosis
Malignant histocytosis
3 Production and maturation blockages
of differentiating cells
DNA synthesis blockage, Vit B12,falic
acid difficiencies,嘌呤和嘧啶
metabolic defects→Megaloblastic
anemia
Hb synthesis blockage,
Heme production defect, IDA
Heptoglobin production defect,
Thalassemias
4 Unknown reason or several
mechanisms
Sideroblastic anemia
Chronic disease anemias (chronic
inflummation,infections,尿毒症,
Hepatic disorders,neoplasm,
connective tissue disease,endocrine
disorders)
二,Accelerated destruction of red cells
1) Endogenous (intra-erythrocyte defects)
1.Membrane defects of erythrocytes,
Hereditary,Hereditary spherocytosis (HS)
Hereditasy elliplocytosis (HE)
Acquired, PNH
2.Enzyme defects
Glucose--6--Phosphate Dehydrogenase
(G6PD) deficiency
Pyruvate kinase deficiency
3.Abnormal haptogllbin synthesis,
Sickle cell anemia,Hemoglobinopathies
Thalassemias
2)Extragenous
1,Immune HA, AIHA,neonatal HA,mismatched
transfusion,drug-induced HA
2,Mechanical, march hemoglobinuria,cardiac
valves prostheses,microangiopathic hemolytic
disorders.
3,Due to chemical,physical or microrganisms,
Chemical toxin-and drug-induced hemolysis,
large scale burned patient (severe burned patient)
Infection-induced,benzene,radiation
microrganisms,Malaria,virus,etc.
4,Increased damage of monocyte-macrocyte system,
Hypersplenism
三, Blood loss
◆ Acute posthemorrage anemia
◆ Chronic bleeding →IDA
Classified accordind to the
proliferative situations of BM
Hyperplastic anemias (增生性贫血 ):
Hemolytic anemia
Anemia caused by blood loss
Megaloblastic anemia,IDA
Hypoplastic anemias (增生减低性贫血 ),AA
Clinical manifestations
Factors influencing symptoms:
Severity of anemia
Hb<80~90g/L→symptoms
Rapidity of anemia
Abrupt loss of 20% of the circulating
blood volume → marked pallor,
postural hypotension and tachycardia
(心动过速 )
The loss of 50% → severe shock even
dealth.
In contrast,the gradual loss
(even Hb 30~40g/L) of the
circulating red cell mass in a
patient with pernicious anemia
may occur without any
symptoms at all.
Why?
? Red cell 2,3 DPG
(RBC内 2,3-二磷酸甘油酸) ↑
In anemia the oxyhemoglobin dissociation curve
usually shifts (右移 ) in a manner to increase the
quantity of oxygen released in tissues without
oppeciably altering the quantity of osygen bound in
the lungs,Red cell 2,3 diphophoglycerate (2,3 DPG)
regularly increases in anemic patients to mediate
this effect,Maximum elevation of RBC 2,3 DPG
increases oxygen delivery only about 30 per cent,
but this is a highly efficient form of compensation
requiring no significant expenditure of energy.
The aged patients or patients
with vascular or cardiac diseases
may not stand to milder anemia.
The level of anemia at which
symptoms occur is highly variable
among individuals as would be
expected from the widely differing
degrees of physical activity,physical
conditioning,circulatory adequacy,
and sensitivity or stoicism of the
population,
1,General manifestations:
(Nonspecific and reflect tissue hypoxia)
Tiredness,fatigue→ the most common,the
earliest symptom
Pallor of skin and mucosa→shared
chracteristic
2, Cardiovascular systems,
Palpitations and dyspnea on exertion,
breathlessness→common symptoms
Valvulae murmurs
Hb <30g/L,>3m→Anemic cardic disease
3,Neurologic system,
Headache,Dizziness,Confusion,decreased
mental acuity (记忆力衰退 ),晕厥,注意力
不集中,失眠,耳鸣.
severe anemia→Coma
4, Digestive system:
Anorexia (食欲不振 ),厌食 →early
megaloblastic anemia
Nausea(恶心 ),flatulence(胀气 ),
diarrhoea(腹泻 ) or constipation (便秘 )
lingual abnormalities (舌的改变 ),common
5,Genitourinary system:
severe anemia→ polyurea (多尿 ),
hypobaric urine (尿比重低 ),
proteinuria (蛋白尿 ),肾小球滤过功能和小
管分泌及回收功能障碍
female:disturbed menstruation (月经紊
乱 ),性功能减退多见
6,Other:
7,Manifestations of underlying disease:
The process of correct diagnosis is the
one of differential diagnosis.
Steps,1,To Establish the type of
anemia
2,To find out the cause or
underlying diseases of anemia
Diagnosis
1,Cause or inducer of anemia:
Nutrition,special habits for food change in
stool habits,stool Guaiacs in all
profession
influation of surrounding environment
chronic diseases
menstruation,marriage
一,History
2,Developing processes,severity
& complications of anemias
Duration and onset of symptoms
3.Important laboratory results,
diagnosis,treatments and their
effects.
skin and mucosa,pallor,jaundice,
petechiae
hair and nails
adenopathy (淋巴结肿大 )
hepatomegaly-splenomegaly
neurologic abnormalities
肛门及妇科盆腔检查
二,Physical examination
1,The hemogram ( 血像)
Routine blood exam(Hb,RBC)
The reticulocyte count (RC)
RC↑:hyperplastic
RC↓:hypoplastic
三,Laboratory findings
Reticulocyte Count
? Normal,0.002-0.015
? Is required in the evaluation of all patients
with anemia as it is a simple measure of
production
? Young RBC that still contains a small amount
of RNA
? Normally take 1 day for reticulocyte to mature,
Under influence of epo takes 2-3 days
? 1/120th of RBC normally
Absolute Retic count
? Retic counts are reported as a percentage,
RBC count x Retic % = Absoulte retic count
normal,(77+23) x 109/L
? Absolute Retic counts need to be corrected
for early release ( If polychromasia is present)
? Absolute retic/2 (for hct in mid 20’s)
? Absolute retic/3 (hct <20)
MCV(the mean corpuscular volume),the
most useful of the RBC indices.
MCH,MCHC,are rarely as helpful as the
MCV
The leukocyte and platelet count,
Anemia with a diminished
leukocyteand platelet count-pancytopenia-
suggests either primary marrow disease,
megaloblastic anemia,or hypersplenism.
Examination of the peripheral blood smear:
2,Examination of bone marrow
骨髓涂片检查:主要观察 BM增生程度,各系统细胞分类
计数,异常细胞,正常 BM组织有核细胞与脂肪组织各占
1/2,前者增多(尤其是红系)见于增生性贫血,后者增
多代表 BM增生低下,见于 AA,骨髓小粒是血液稀释与
否的一个重要标志。
Examination of aspirated smears in general gives
superior cytologic information while the core
biopsy provides crucial information concerning
the overall cellularity,as well as the presence of
fibrosis,tumor,or granulomas,Both procedures
are complemantary and are best performed
together when the diagnosis is in doubt,Bone
marrow iron staining
3,Some useful ancillary tests
1) Stools for occult blood
2) Tests for hemolytic anemia such as
Coombs’test
3) Tests for nutritional anemia such as serum
folic acid,serum Vitamin B12,SI,SF,etc.
4) Liver and kidney function tests
5) Immunologic tests
6) 影像学检查:钡餐透视,钡灌肠
Treatment
一,Treatment of the causes
The purpose is the treatment
of the underlying disease.
Gastric cancer→Pernicious anemia( 恶性贫血)
( megaloblastic anemia)
二,Drugs
明确病因之前且忌乱投药
? Iron agents; calculation of dose
? falic acid,Vit B12
? Vit B6
? Corticosteroids, AIHA,AA,PNH
? Androgens,may promate reythropoiesis,
1.)刺激 EPO分泌。 2)增强 BM对 EPO的效应。
? EPO,Anemia caused by kidney diseases
? Immunosuppression agents
ALG (antilymphocyte globulin)
CsA,Acute and severe AA
三,Transfusions
Avoid of complications as hepatitis
and AIDS
? Whole blood
? Frozed red cells
? Washed red cells
? Leukocyte poor packed cells ( 浓缩 RBC)
Chronic anemia, Hb<60g/L→Transfusion
Hereditary spherocytosis
AIHA
Hypersplenism
由于胸腺瘤 (Thymoma)引起的纯红 AA,
切除胸腺可使部分患者病情缓解。
Chronic ITP
四,(Operation) Splenectomy
五,BMT( bone marrow
transplantation)
? SAA
? MDS
Lab Evaluation of
Hypoproliferative Anemias
Fe TIBC Ferritin
Fe Deficiency low High(>300) low
Anemia of
Chronic Dx
low low Normal to
high
Aplastic anemia High Extremely
high
Normal to
high
Laboratory findings in anaemia
Drs Shepherd,Dexter,and
Rapson Spring 2001
Scanning Electron microscopy:
normal red cell